Alnylam’s RNAi therapeutic expanded by FDA in advanced primary hyperoxaluria type 1

Alnylam Pharmaceuticals’ label expansion for Oxlumo (lumasiran), an RNAi therapeutic administered via subcutaneous injection, has been approved by the US Food and Drug Administration (FDA) for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary oxalate (UOx) and plasma oxalate (POx) levels in paediatric and adult patients, the company announced.

PH1 is an ultra-rare genetic disease characterised by oxalate overproduction in the liver, resulting in the deposition of calcium oxalate crystals in the kidneys and urinary tract. This can lead to the formation of painful and recurrent kidney stones and nephrocalcinosis, which can progress to kidney failure.

The disease can also lead to oxalate deposition in multiple organs beyond the kidney, a condition known as systemic oxalosis.

Oxlumo was approved by the FDA for the treatment of PH1 to lower UOx levels in paediatric and adult patients in November 2020, and was also approved by the European Medicines Agency for the treatment of PH1 in all age groups.

The FDA’s latest decision is based on positive results from the phase 3 ILLUMINATE-C study of Oxlumo in patients with severe renal impairment, in which Oxlumo treatment resulted in substantial reductions in POx and demonstrated an encouraging safety and tolerability profile in patients with compromised renal function, including those with kidney failure and undergoing treatment by haemodialysis.

Elevated POx is directly related to the pathophysiology of oxalosis, the company outlined, and results in systemic deposition of oxalate in extra-renal tissues, potentially leading to bone fractures, cardiomyopathy, impaired erythropoiesis, vision loss, skin ulcers and other serious manifestations.

Also included in the supplemental new drug application were results from the open-label extensions of the ILLUMINATE-A and ILLUMINATE-B phase 3 studies of paediatric and adult patients with PH1.

Jorge Capapey, vice president, global rare disease lead at Alnylam Pharmaceuticals, said: “Today’s label expansion exemplifies Alnylam’s commitment to advancing research and innovation in support of the PH1 community. We also believe this expansion will strengthen prescribers’ confidence in Oxlumo for patients.

“Through the findings of the ILLUMINATE clinical development programme, I am thrilled to see the potential benefit of Oxlumo, which remains the first and only FDA-approved PH1 treatment option, now be available for a broad range of people living with the ultra-rare disease, including those advanced PH1 patients undergoing haemodialysis.”